ABSTRACT
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that affects social interaction and behavior. Mutations in the gene encoding chromodomain helicase DNA-binding protein 8 (CHD8) lead to autism symptoms and macrocephaly by a haploinsufficiency mechanism. However, studies of small animal models showed inconsistent findings about the mechanisms for CHD8 deficiency-mediated autism symptoms and macrocephaly. Using the nonhuman primate as a model system, we found that CRISPR/Cas9-mediated CHD8 mutations in the embryos of cynomolgus monkeys led to increased gliogenesis to cause macrocephaly in cynomolgus monkeys. Disrupting CHD8 in the fetal monkey brain prior to gliogenesis increased the number of glial cells in newborn monkeys. Moreover, knocking down CHD8 via CRISPR/Cas9 in organotypic monkey brain slices from newborn monkeys also enhanced the proliferation of glial cells. Our findings suggest that gliogenesis is critical for brain size in primates and that abnormal gliogenesis may contribute to ASD.
ABSTRACT
BACKGROUND: Topical Chinese herbal medicine (CHM) is generally used in China, separately or in combination with conventional medicine, to treat diabetic peripheral neuropathy (DPN). Clinical studies have shown beneficial effects of CHM compared with conventional medicine. MATERIALS AND METHODS: A systematic literature search of Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, AMED, Chinese BioMedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI) and Chinese Scientific Journal Database (VIP) information was conducted till March 2010. Randomized controlled trials (RCTs) were included if they compared topical CHM to conventional medicine, placebo or no treatment for patients with DPN. Revman 5.0.17 was used as software for data analysis. The effect expectancy is depicted as relative risk and mean difference with a 95% confidence interval. RESULTS: 23 RCTs including 22 topical CHMs were included. The methodological quality of the included trials is generally poor in terms of sequence generation, concealment of allocations, blinding, incomplete data outcome and selective outcome reports. 17 trials showed beneficial effects of CHM on global symptom improvement, 6 beneficial effects of CHM on nerve velocity conduction, 4 beneficial effects of CHM on numbness improvement and 4 beneficial effects of CHM on pain relief. Adverse events with relation to CHM were reported in 3 trials including skin redness, a burning feeling, a prickling sensation and rash. CONCLUSIONS: Due to weak evidence, the claimed benefits of topical CHM for DPN are inconclusive; more stringent studies are needed to support clinical practice.
